Antioxidant Properties Research Articles

Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies.

In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1. BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Red-cell omega-3 fatty acids associate with increased hippocampal volume and superior longitudinal cognition in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Omega-3 Fatty Acids (n-3 FAs) have anti-thrombotic, anti-inflammatory and anti-oxidative properties; however, their neuroprotective effects remain controversial. Here, we report the association of n-3 FAs with both structural (hippocampal volume) and functional (cognition) readouts in a large cohort of AF pts. Purpose a) To determine the association of n-3 FAs and left and right hippocampal volume at baseline in AF pts. b) To assess the predictive value of HV and n-3 FAs for the risk of cognitive impairment after a 7-year follow-up period. Methods This prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF) included 2,359 pts with documented AF and baseline red-cell n-3 FAs levels, measured by gas chromatography and mass spectrometry. Hippocampal volume (HV) and segmentation based intracranial volume (ICV) were analyzed by FreeSurfer's (v 7.4.0) subregion segmentation module and Sequence Adaptive Multimodal SEGmentation from brain MRI in 1,736 pts. Detailed neurocognitive assessments in pts at baseline and follow up periods were performed. We used mixed-effect linear regression models to determine the association of n-3 FAs and HV. For conversion to cognitive impairment (defined as MoCA score < 26), we performed cox-proportional hazards regression model. Two adjustment models were applied as described in the figures. Results Patients with AF (mean age, 73 years old [±8.5 SD]; 157 women [27%]) with 9569 cognitive evaluations (mean follow-up, 3.6 years [±2.3 SD]) were assessed. At baseline, we observed statistically significant associations between total n-3 FAs levels (EPA + DHA + ALA + DPA) and individual n-3 FAs (EPA, DHA, DPA) with increased HV after adjustment for ICV and other covariates (Fig1A, 1B). After all adjustments, EPA remained associated with both bilateral HV and right HV. Furthermore, we observed a significant association between HV and neurocognitive assessments, as measured both in global (MoCA, CoCo) and specific tests (TMT-A, TMT-B, DSST, SF) (Fig1C). Over time, quartile 4 (Q4, highest n-3) compared to quartile 1 (Q1, lowest), had a 16% lower risk of cognitive impairment (HR, 0.84 [CI 0.75-0.93]; P=0.001) for total n-3 FAs and even 30% lower specifically for EPA (HR, 0.7 [CI 0.63-0.78]; P<0.001). The risk of cognitive impairment was 47% lower (HR, 0.53 [CI 0.45-0.63]; P<0.001) when the highest HV Q4 was compared to lowest HV Q1 (Fig2A). In combination, the highest quartile of bilateral HV and EPA demonstrated an increased probability of being cognitive impairment-free and they had a 72% lower (HR, 0.28 [0.18-0.43]; P<0.001) risk of cognitive impairment (Fig2B). Conclusions 1. Red cell n-3 FAs levels are associated with higher HV in AF pts. 2. Higher baseline levels of n-3 FAs, particularly of EPA, are associated with both an increased HV and a decreased risk of cognitive impairment after 7 years follow up.

Role of vitamin K2 and vitamin K cycle enzymes in aortic valvular interstitial cell calcification

Abstract Introduction Calcific aortic valve disease (CAVD) is the most common valve disease. Currently, there is no medical treatment available for CAVD. Vitamin K antagonists promote CAVD while population-based studies suggest that dietary intake of vitamin K reduces the incidence of CAVD in adults. However, randomized trials have so far not proven a clear benefit of vitamin K supplementation on the progression of AVS. Consequently, there is a need for a deeper understanding of the role of vitamin K in valvular calcification. This study aims to further investigate mechanisms of action of vitamin K during valvular calcification. Methods and Results Aortic valve samples were obtained from patients undergoing surgical aortic valve replacement for CAVD and valvular interstitial cells (VIC) were isolated by collagenase II digestion (Fig. 1). VIC expressed typical markers like Vimentin and α-SMA and were cultured in a control medium (CM) or further calcified in a pro-calcifying medium (PCM) containing sodium dihydrogen phosphate and ascorbic acid. PCM led to upregulation of Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) expression, and ALP-activity after 7 and 21 days of culture. Moreover, alizarin red staining visualized significant calcium mineral deposition after 21 days of culture (Fig. 2). The addition of the most potent vitamin K2 derivative (Menaquinone-7, MK-7) improved cell viability under both control and calcifying conditions (Fig. 3). Moreover, MK-7 protected VIC from ferroptotic cell death (Fig. 4) and increased expression of the vitamin K-dependent Matrix-Gla-protein (MGP), a major inhibitor of ectopic calcification (Fig. 5). To fulfill its function as an activator of vitamin K-dependent proteins like MGP, vitamin K needs to be reduced to vitamin K hydroquinone by the vitamin K epoxide reductase enzymes VKORC1 and VKORC1L1. In VIC, using our calcification protocol, treatment with PCM led to the downregulation of VKORC1, but not of VKORC1L1, an enzyme with known anti-oxidative properties (Fig. 6). We next performed siRNA-mediated knockdown of VKORC1 and VKORC1L1 in VIC and observed calcification after 7 and 21 days of culture by measuring expression of ALP, RUNX2, quantifying ALP activity, and staining for calcium minerals (alizarin red). Intriguingly, VKORC1L1-knockdown sharply increased the expression of ALP. To further elucidate these findings, we will perform overexpression experiments to analyze, if VKORC1L1 can alleviate PCM-induced calcification Conclusion: Vitamin K2 inhibits in vitro calcification of valvular interstitial cells and upregulates the calcification inhibitor Matrix-Gla-Protein. Our results suggest the involvement of the vitamin K cycle enzyme VKORC1L1, which is known to exhibit anti-oxidative and cytoprotective effects. Further studies are warranted to shed light on the regulation of the enzymes to improve our understanding.

The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1

The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease.

Zaluzanin-D enriched Vernonia arborea extract mediated copper oxide nanoparticles synthesis and their anti-oxidant, anti-inflammatory and DNA methylation altering properties.

Metal oxide nanoparticles synthesized with the aid of medicinal plant extracts are showing potential as treatment options for inflammatory diseases. Two key benefits of this synthesis method is: the synthesis process is environmentally benign and the utilization of medicinal plant-derived extracts adds to the medicinal value of the synthesized nanoparticle. Earlier, sesquiterpene lactone zaluzanin-D (ZD) has been isolated from leaves of Vernonia arborea. ZD showed ability to reduce inflammation in activated monocytes. Copper oxide nanoparticles (bCuO-NPs) were synthesized using ZD-enriched leaf extract of V. arborea and characterized by UV-vis spectroscopy, FT-IR, XRD, particle size analyzer, and TEM. Synthesized bCuO-NPs did not show significant toxicity to human monocytic cell lines (THP-1) at the tested concentrations. The bCuO-NPs showed radical scavenging ability indicating anti-oxidant properties. Flow cytometry experiments proved the capability of bCuO-NPs to reduce intracellular ROS in peroxide-activated THP-1 cells. The NPs also showed a significant ability to reduce inflammatory adhesion in PMA-activated THP-1 cells. In the DNA methylation studies, bCuO-NPs behaved similarly to ZD and prevented DNA hypomethylation at the MMP-9 promoter region. These properties strongly indicate the ability of bCuO-NPs to reduce inflammation in the activated monocytes. Furthermore, in zebrafish (Danio rerio) embryos, the developmental toxicity of bCuO-NPs was assessed. The studies indicated the reduced toxicity and compatibility of the NPs with biological organisms. Based on the results, it can be concluded that the bCuO-NPs produced from ZD-enriched leaf extract have significant anti-oxidant capabilities and the ability to reduce inflammation in monocytic cell lines. Overall, reduced in vitro and in vivo toxicity, along with its antioxidant and anti-inflammatory properties, makes bCuO-NPs a potential candidate for anti-inflammatory drugs.

Coloprotective effects of chebulic myrobalan extract by regulation of AMPK-SIRT1 signaling: A pharmacological and histopathological evaluation

Ulcerative colitis is a chronic, refractory disease caused by dysregulation of mucosal immune responses to the indigenous bacterial flora as well as genetic and environmental variables. Recently, there has been increasing interest towards the use of herbal medicines for the treatment of ulcerative colitis and the potential benefits could lie in their high patient acceptability, effectiveness, safety, and relatively low cost. It has been reported that Chebulic myrobalan (Terminalia chebula) exhibits anti-oxidant, anti-inflammatory and immunomodulatory properties. The present study was designed to evaluate the protective potential of extract of dried fruit pulp of T. chebula against Dextran sulphate sodium (DSS)-induced ulcerative colitis in male BALB/c mice. Three cycles of DSS (3 % w/v in drinking water), each followed by a seven-day remission phase were used to induce ulcerative colitis in mice. Animals were treated with T. chebula (300 mg/kg and 600 mg/kg) starting from Ist remission period to the end of the study. Different biochemical assays, histological evaluation and molecular analysis were performed to evaluate the protective effects of T. chebula extract in DSS induced colitis. T. chebula modulates the expression of nuclear factor kappa B, adenosine monophosphate kinase, tumour necrosis factor-alpha, sirtuin 1 and interleukin-1β. Furthermore, it also accorded coloprotective effects against DNA damage, apoptosis, inflammation and nitrosative stress. Finally, it was found that the high dose of the T. chebula extract (600 mg/kg) was found to be more effective than a low dose (300 mg/kg) in restoring the ulcerative colitis induced colonic damage.

Diammonium glycyrrhizinate ameliorates alcohol-induced liver injury by reducing oxidative stress, steatosis, and inflammation

Alcohol-induced liver injury (ALI) is a serious global health issue. Diammonium glycyrrhizinate (DG), a pharmaceutical form of glycyrrhizic acid, has been reported to have anti-inflammatory and anti-oxidative stress properties. We investigated the potential hepatoprotective effects of DG against ALI and explored the mechanisms of it. In vivo, C57BL/6J mice were used to investigate the protective effect of DG on ALI induced by chronic plus binge alcohol exposure. In vitro, AML-12 cells were applied to evaluate the role of DDX5 in the hepatic protection of DG and explore the possible mechanism of STAT1 activation regulated by DDX5. The results showed that DG significantly alleviated liver injury, inflammation, and lipid deposition in hepatocytes. It also beneficially influenced oxidative stress dysregulation. RNA-seq expression in mouse liver tissue indicated that Dead-box helicase 5 (DDX5) might be a potential target of DG. Compared with the control group, the expression of DDX5 decreased significantly in the ethanol-fed group, while DDX5 was restored in the DG treatment group. In addition, the protective effects of DG against ALI were impaired by DDX5 deficiency. DDX5 inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1) by recruiting the protein inhibitor of activated STAT1 (PIAS1) to STAT1. The protective effect of DG against ALI associated with oxidative stress, steatosis, and inflammation was probably via regulating the DDX5/STAT1 axis.

Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

The Effect of Aloe vera on Skin and Its Commensals: Contribution of Acemannan in Curing Acne Caused by Propionibacterium acnes

Aloe vera is one of the most significant therapeutical plant species that belongs to the family Liliaceae. Aloe vera is composed of a high amount of water, with the remainder being dry matter. The dry matter contains a lot of bioactive compounds like carbohydrates, fats, and enzymes, with various therapeutic and antimicrobial properties. It can enhance the proliferation of cells and prevent cell damage by anti-oxidative properties (stimulating the secretion of superoxide dismutase and peroxidase). Human skin is colonized by microbes like fungi (Candida albicans), bacteria (Propionibacterium acnes, Staphylococcus aureus), and mites. These commensals are responsible for skin characteristics such as acidic pH, the pungent smell of sweat, etc. Human fetuses lack skin microbiota, and their skin is colonized after birth. Commensals present on the skin have a crucial role in training the human immune system against other pathogenic microbes. Propionibacterium acnes act as an opportunistic pathogen when the balance between the commensals is disturbed. We also emphasize the recent progress in identifying the aloe metabolite biosynthesis pathways and the associated enzyme machinery. The hyperproliferation of Propionibacterium acnes causes acne, and acemannan plays a significant role in its cure. Hence, we need to consider a new treatment approach based on the root cause of this dysbiosis.

Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin–eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

Anticancer Properties Against Select Cancer Cell Lines and Metabolomics Analysis of Tender Coconut Water.

Tender Coconut Water (TCW) is a nutrient-rich dietary supplement that contains in bioactive secondary metabolites and phytohormones with anti-oxidative and anti-inflammatory properties. Studies on TCW's anti-cancer properties are limited and the mechanism of its anti-cancer effects have not been defined. In the present study, we investigate TCW for its anti-cancer properties and, using untargeted metabolomics, we identify components form TCW with potential anti-cancer activity. Cell viability assay, BrdU incorporation assay, soft-agar assay, flow-cytometery, and Western blotting were used to analyze TCW's anticancer properties and to identify mechanism of action. Liquid chromatography- Tandem Mass Spectroscopy (LC-MS/MS) was used to identify TCW components. TCW decreased the viability and anchorage-independent growth of HepG2 hepatocellular carcinoma (HCC) cells and caused S-phase cell cycle arrest. TCW inhibited AKT and ERK phosphorylation leading to reduced ZEB1 protein, increased E-cadherin, and reduced N-cadherin protein expression in HepG2 cells, thus reversing the 'epithelial-to-mesenchymal' (EMT) transition. TCW also decreased the viability of Hep3B hepatoma, HCT-15 colon, MCF-7 and T47D luminal A breast cancer (BC) and MDA-MB-231 and MDA-MB-468 triplenegative BC cells. Importantly, TCW did not inhibit the viability of MCF-10A normal breast epithelial cells. Untargeted metabolomics analysis of TCW identified 271 metabolites, primarily lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic oxygen compounds. We demonstrate that three components from TCW: 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, iondole-3-carbox aldehyde and caffeic acid inhibit the growth of cancer cells. TCW and its components exhibit anti-cancer effects. TCW inhibits the viability of HepG2 hepatocellular carcinoma cells by reversing the EMT process through inhibition of AKT and ERK signalling.

Anti-Aging Activities and LC-MS Analysis of Chrysophyllum cainito Leaves Extract

Star apple (Chrysophyllum cainito L.), or Apple-nam in Thai, is a medium-sized tree in the Sapotaceae family. It is native to Middle America and distributed in Thailand and Southeast Asia. It has antioxidation, anti-inflammatory and anti-diabetic properties. The active compounds in star apples are flavonoids. This research aimed to study the biological activities and chemical constituents of crude extract and active fractions from the leaves of star apples. The leaf powder was defatted with dichloromethane and further extracted with ethanol using ultrasound-assisted extraction. The ethanol extract was separated by quick column chromatography given 7 fractions (CCE1-CCE7). The total phenolic content and antioxidant activity of the extract and chromatographic fractions were determined. The active fractions were further studied for tyrosinase inhibition, collagenase inhibition and cell proliferation properties. The result showed that the highest total phenolic content was observed in ethanol extract. The high polar fraction, CCE6, displayed the highest antioxidation activity with radical scavenging of 0.34 ± 0.01 mg AAE/mL in the DPPH assay and a FRAP value of 1.36 ± 0.01 mg AAE/mL in the FRAP assay. The CCE6 also exhibited the highest anti-tyrosinase and anti-collagenase activities with a percentage of 67.14 ± 1.34 and 70.32 ± 2.88, respectively and showed the best activity in cell proliferation with a percentage of 24.68 ± 2.94. The analysis of the components using the negative ionization LC-MS technique revealed that gallic acid and quercetin-3-galactoside are the major constituents in the ethanol extract. While the fraction CCE6 showed glucosyl (2E,6E,10x)-10,11-dihydroxy-2,6-farnesadienoate and p-mentha-1,3,5,8-tetraene as the predominant compounds. HIGHLIGHTS The ethanol extract was prepared using ultrasound-assisted extraction. The first report of tyrosinase and collagenase inhibition, as well as cell proliferation properties, of the cainito leaves extract and chromatographic fractions. The major components of the ethanol extract of cainito leaves in Thailand and its active fraction by LC-MS technique were reported for the first time. GRAPHICAL ABSTRACT

Comparative study of chemical constituents and biological potency in Lantana camara Linn. leaf essential oil collected from two different sites in Northeast India

The ubiquitous occurrence of Lantana camara highlights its exceptional ecological versatility. Leaves of L. camara were obtained for this study from two different locations of NE, India. Hydro distillation was used to extract the essential oils from the leaves, and gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID) were used to study the chemical profiles of the isolated oils. The essential oil analysis detected 35 components in total essential oil from Location 1 (BLCEO) while in Location 2 essential oil (JLCEO), 29 components were identified. Caryophyllene, humulene and sabinene were present in considerably major amounts in both BLCEO and JLCEO, though variation in area percentage was seen. The anti-oxidant properties of BLCEO were better than that of JLCEO. The BLCEO has also exhibited better results in inhibiting acetylcholinesterase. However, both the essential oils did not show any prominent results in α-amylase inhibitory assay and anti-tyrosinase activity. In this study, the phytochemical composition and their effect on the bioactivity of both samples were observed. The chemical constitution of L. camara essential oils (LCEO) and its possible ecological ramifications have also been well explained.

Physicochemical, Textural, and Antioxidant Attributes of Yogurts Supplemented with Black Chokeberry: Fruit, Juice, and Pomace.

The fruit, juice, and pomace of black chokeberry (Aronia melanocarpa) are a rich source of phenolic compounds and can be used to obtain enriched dairy products. Chokeberry fruit, due to its astringent taste, is less favorable or even unacceptable to consumers and is usually processed into juice, resulting in large quantities of pomace, which is often discarded as waste. The aim of this study is to valorize chokeberry fruit, juice, and pomace by incorporating them in different percentages (1, 2, and 3%) into yogurt as functional ingredients. The physicochemical (total solids content, fat, protein, titratable acidity, pH, color), textural (hardness, adhesion, cohesiveness, springiness, gumminess, and chewiness), antioxidant (DPPH scavenging activity and total phenolic content), and sensory characteristics of supplemented yogurts were investigated. The results showed that the addition of chokeberry pomace in yogurt increased their total solids content (from 11.46 ± 0.18% for the plain yogurt sample to 13.71 ± 0.18% for the yogurt sample with 3% chokeberry pomace), while the addition of fruit and juice decreased the protein content of the yogurt samples (from 4.35 ± 0.11% for the plain yogurt sample to 3.69 ± 0.15% for the yogurt sample with 3% chokeberry fruit and to 3.84 ± 0.1% for the yogurt sample with 3% chokeberry juice). There was no statistically significant change in the fat content of all samples of chokeberry-supplemented yogurt compared to plain yogurt. The pH of the yogurt samples decreased with the increase in the percentage of chokeberry fruit, juice, and pomace added to the yogurt (from 4.50 for the plain yogurt samples to 4.35, 4.30, and 4.20 for the yogurt samples supplemented with 1, 2, and 3% black chokeberry pomace). Inhibition of DPPH radical formation was higher in the yogurt samples with chokeberry fruit (57.84 ± 0.05%, 73.57 ± 0.11%, and 75.38 ± 0.05% inhibition for the samples with 1, 2, and 3% fruit) and pomace (up to 64.8 ± 0.11% inhibition for the sample with 3%), while total phenolic content decreased (from 392.14 ± 2.06 to 104.45 ± 2.63 µg/g) as follows: yogurt with chokeberry pomace > yogurt with chokeberry fruit > yogurt with chokeberry juice. The yogurt samples with the highest acceptance scores were the samples with 3% and 2% black chokeberry fruit, while the lowest acceptance score was obtained for the yogurt sample with 3% black chokeberry pomace. Chokeberry fruit, juice, and pomace can improve the physicochemical, textural, and antioxidant characteristics of yogurt, emphasizing that the antioxidant effect of yogurt could be substantially improved by the addition of chokeberry pomace due to its high phenolic content, while incorporation into yogurt is another way to valorize this by-product.

Mannose coated selenium nanoparticles normalize intestinal homeostasis in mice and mitigate colitis by inhibiting NF-κB activation and enhancing glutathione peroxidase expression

Impaired intestinal homeostasis is a major pathological feature of inflammatory bowel diseases (IBD). Mannose and selenium (Se) both demonstrate potential anti-inflammatory and anti-oxidative properties. However, most lectin receptors bind free monosaccharide ligands with relatively low affinity and most Se species induce side effects beyond a very narrow range of dosage. This has contributed to a poorly explored therapies for IBD that combine mannose and Se to target intestinal epithelial cells (IECs) for normalization gut homeostasis. Herein, a facile and safe strategy for ulcerative colitis (UC) treatment was developed using optimized, mannose-functionalized Se nanoparticles (M-SeNPs) encapsulated within a colon-targeted hydrogel delivery system containing alginate (SA) and chitosan (CS). This biocompatible nanosystem was efficiently taken up by IECs and led to increased expression of Se-dependent glutathione peroxidases (GPXs), thereby modulating IECs’ immune response. Using a mouse model of DSS-induced colitis, (CS/SA)-embedding M-SeNPs (C/S-MSe) were found to mitigate oxidative stress and inflammation through the inhibition of the NF-kB pathway in the colon. This stabilized mucosal homeostasis of IECs and ameliorated colitis-related symptoms, thereby providing a potential new approach for treatment of IBD.

The Effect of Nerolidol on Renal Dysfunction following Bilateral Ureteral Obstruction.

Background/Objectives: Obstructive uropathy is a common cause of renal impairment. Recently, there has been a burgeoning interest in exploring natural products as potential alternative remedies for many conditions due to their low toxicity, affordability and wide availability. Methods: We investigated the effect of nerolidol in a rat model of bilateral ureteral obstruction (BUO) injury. Nerolidol, dissolved in a vehicle, was administered orally as a single daily dose of 200 mg/kg to Wistar rats. Sham group (n = 12) underwent sham surgery, whereas the BUO (n = 12) and BUO/NR groups (n = 12) underwent reversible 24-h BUO and received the vehicle or nerolidol, respectively. The treatment started 9 days prior to the BUO/sham surgery and continued for 3 days after reversal. Renal functions were assessed before starting the treatment, just prior to the intervention and 3 days after BUO reversal. Results: Neither nerolidol nor the vehicle affected the basal renal functions. Nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also attenuated the changes in several markers associated with renal injury, inflammation, apoptosis and oxidative stress and mitigated the histological alterations. Conclusions: The findings of this study demonstrated the potent reno-protective effects of nerolidol in mitigating the adverse renal effects of bilateral ureteral obstruction. This is attributed to its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-oxidant properties. These effects were reflected in the partial recovery of renal functions and histological features. These findings may have potential therapeutic implications.

Polysaccharide of Dicliptera chinensis (L.) Juss. alleviated cholestatic liver disease by modulating the FXR pathway

Dicliptera chinensis (L.) Juss., is an herb known for its anti-inflammatory and anti-oxidant properties. In the previous studies, the chemical composition of the polysaccharide from Dicliptera chinensis (L.) Juss. (DCP) has been characterized as consisting of DCP1 and DCP2, of which DCP2 has hepatoprotective effects. The study examined the hepatoprotective potential of DCP2 against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver disease (CLD). In this study, RNA sequencing identified key research pathways involving bile acid metabolism, oxidative stress, and inflammation. Furthermore, qRT-PCR and Western blot analyses were conducted to further characterize these pathways. Additionally, the study included in vitro experiments with HepG2 cells to further investigate the effects of DCP2 on bile acid metabolism. In summary, the protective effect of DCP2 on the liver was reflected in alleviating the inflammatory response and oxidative stress, regulating the metabolism of bile acids, and mitigating liver damage caused by bile acids. This study further elucidated the hepatoprotective effects of DCP2 by examining its ability to counteract ANIT-induced CLD, suggesting that DCP2 is a promising biomacromolecule for hepatoprotection.

Leonurine Inhibits Hepatic Lipid Synthesis to Ameliorate NAFLD via the ADRA1a/AMPK/SCD1 Axis.

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt., and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (Scd1), Spermine Synthase (Sms), AP-1 Transcription Factor Subunit (Fos), Oxysterol Binding Protein Like 5 (Osbpl5), and FK506 binding protein 5 (Fkbp5) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.

Protective effect and mechanism of lycium barbarum polysaccharide against UVB-induced skin photoaging.

Cellular senescence can be categorized into two main types, including exogenous and endogenous aging. Photoaging, which is aging induced by ultraviolet (UV) radiation, significantly contributes to exogenous aging, accounting for approximately 80% of such cases. Superoxide Dismutase (SOD) is a class of antioxidant enzymes, with SOD2 being predominantly localized in the mitochondrial matrix. Ultraviolet radiation (UVR) inhibits SOD2 activity by acetylating the key lysine residues on SOD2. Sirtuin3 (SIRT3), the principal mitochondrial deacetylase, enhances the anti-oxidant capacity of SOD2 by deacetylating. Lycium barbarum polysaccharide (LBP) is the main bioactive component extracted from Lycium barbarum (LB). It has been reported to have numerous potential health benefits, such as anti-oxidation, anti-aging, anti-inflammatory and anti-apoptotic properties. Furthermore, LBP has been shown to regulate hepatic oxidative stress via the SIRT3-SOD2 pathway. The aim of this study was to construct a UVB-Stress-induced Premature Senescence (UVB-SIPS) model to investigate the protective effects and underlying mechanisms of LBP against UVB-induced skin photoaging. Irradiated with different UVB doses to select the suitable dose for constructing the UVB-SIPS model. Cell morphology was observed using a microscope. The proportion of senescent cells was assessed by senescence-associated β-galactosidase (SA-β-gal) staining. Cell viability was studied using the Cell Counting Kit-8 (CCK-8). Intracellular levels of reactive oxygen species (ROS) were observed using flow cytometry and an inverted fluorescence microscope. Expression of γ-H2AX was investigated using flow cytometry. Western blot (WB) was used to verify the expression of senescence-associated proteins (p21, p53, MMP-1, and MMP-3). Enzyme-Linked Immunosorbnent Assay (ELISA) was used to measure pro-inflammatory cytokines levels (IL-6, TNF-α). WB was also used to analyze the expression of SIRT3, SOD2, and Ac-SOD2, and a specific kit was employed to detect SOD2 activity. Our results suggested that the UVB-SIPS group pre-treated with LBP exhibited a reduced proportion of cells positive for SA-β-gal staining, mitigated production of intracellular ROS, an amelioration in γ-H2AX expression, and down-regulated expression of senescence-associated proteins and pro-inflammatory cytokines as compared to the UVB-SIPS group. Moreover, in contrast to the control group, the UVB-SIPS group showed regulated SIRT3 expression and SOD activity, elevated Ac-SOD2 expression and an increased ratio of Ac-SOD2/SOD2. However, the UVB-SIPS group pre-treated with LBP showed an upregulation of SIRT3 expression and enhanced SOD activity, a reduction in AC-SOD2 expression, and a decreased ratio of AC-SOD2/SOD2, compared to the untreated UVB-SIPS group. Additionally, the photo-protective effect of LBP was diminished following treatment with 3-TYP, a SIRT3-specific inhibitor. This study suggested that LBP, a natural component, exhibits anti-oxidant and anti-photoaging properties, potentially mediated through the SIRT3-SOD2 pathway.

The protective effect of Amitriptyline on experimental colitis through inhibiting TLR4/MD2 signaling pathway.

Amitriptyline, a pleiotropic tricyclic antidepressant, possesses anti-oxidant and anti-inflammatory properties. Despite its diverse benefits, the specific effects of amitriptyline on IBD are not yet well defined. To explore this, we utilized a DSS-induced colitis model to examine the anti-inflammatory effects of amitriptyline and the underlying mechanisms by which it operates. Our research revealed that amitriptyline is effective in alleviating several pathological manifestations associated with colitis. This includes improvements in body weight retention, reductions in DAI, lessening of colon length shortening, and repair of colonic mucosal damage. Treatment with amitriptyline significantly protected mucosal injury by preserving the population of goblet cells and increasing the expression of tight junction proteins. Furthermore, we observed that amitriptyline effectively countered immune cell infiltration, specifically neutrophils and macrophages, while simultaneously lowering the levels of inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Additionally, RNA sequencing analysis pointed to the potential involvement of the TLR pathway in the anti-colitic effects induced by amitriptyline. Subsequent Western blot analysis indicated that amitriptyline significantly inhibited the TLR4-mediated NF-κB signaling pathway. To bolster our findings, in vitro studies demonstrated that amitriptyline down-regulated the TLR4/NF-κB/MAPK signaling cascades in mouse macrophages stimulated with LPS. Further molecular investigations revealed that amitriptyline was able to suppress the elevated expression of MD-2 that LPS stimulation typically induces. In summary, our findings suggest that amitriptyline effectively mitigates DSS-induced colitis in mice through the inhibition of TLR4/MD-2 pathway signaling, indicating its potential repurposing for IBD treatment. Significance Statement The potential of utilizing amitriptyline in treating IBD appears promising, leveraging its established safety and dosing profile as an antidepressant. Our observations show that amitriptyline can alleviate pathological symptoms, inflammation, and intestinal mucosal damage in mice with colitis induced by DSS. The protective effect observed appear to be linked to the inhibition of the TLR4/MD2 signaling pathway. By exploring novel applications for existing medications, we can optimize amitriptyline's efficacy and broaden its impact in both medical and commercial contexts.